CIHM 
Microfiche 
Series 
(■Monographs) 


ICIMH 

Collection  de 
microfiches 
(monographies) 


Canadian  Institute  for  Historical  Microraproductions  /  Institut  Canadian  da  microraproductlons  historiquas 


199 


Technical  and  Biblioflrapltic  Notei  /  Notvs  techniques  et  bibliographiquM 


The  Institute  has  attempted  to  obtain  the  best  original 
copy  available  for  filming.  Features  of  this  copy  which 
may  be  bibliographically  unique,  which  may  alter  any 
of  the  images  in  the  reproduction,  or  which  may 
significantly  change  the  usual  method  of  filming,  are 
chpcked  below. 


L'Institut  a  microfilm^  le  meilleur  exemplaire  qu'il 
lui  a  iti  possible  de  se  procurer.   Les  details  de  cet 
exemplaire  qui  sont  p«ut-4tre  uniques  du  point  de  vue 
bibliographique,  qui  peuvent  modifier  une  image 
reproduite.  ou  qui  peuvent  exiger  une  modification 
dans  la  mithode  normale  de  f  ilmage  sont  indiques 
ci-dessous. 


ca 
0 


Coloured  covers/ 
Couverture  de  couleur 

Covers  damaged/ 
Couverture  endommagto 

Covers  restored  and/or  laminated/ 


I I  Couverture  resUurie  et/ou  pelliculte 


n 


Cover  title  missing/ 

Le  titre  de  couverture  manque 


□  Coloured  maps/ 
Cattes  giographiques  en  couleur 

□  Coloured  ink  (i.e.  other  than  blue  or  black)/ 
Encre  de  couleur  (i.e.  autre  que  bleue  ou  noire) 


D 
0 


D 


n 


Coloured  plates  and/or  illustrations/ 
Planches  et/ou  illustrations  en  couleur 

Bound  with  other  material/ 
Relie  avec  d'autres  documents 

Tight  binding  may  cause  shadows  or  distortion 
along  interior  margin/ 

La  reliure  serree  peut  causer  de  I'ombre  ou  de  la 
distorsion  le  long  de  la  marge  interieure 

Blank  leaves  added  during  restoration  may  appear 
within  the  text.  Whenever  possible,  these  have 
been  omitted  from  filming/ 
It  se  peut  que  certaines  pages  blanches  aiouttes 
lors  d'une  restauration  apparaissent  dans  le  texte, 
mais,  lorsque  cela  etait  possible,  ces  pages  n'ont 
pas  ete  filmees. 


Additional  comments:/ 
Commentaires  supplementaires: 


This  Item  is  filmed  at  the  reduction  ratio  checked  below/ 

Ce  document  est  filme  au  taux  de  reduction  indiqui  ci-dessous. 

10X  14X  18X 


□  Coloured  pages/ 
Pages  de  couleur 

□  Pages  dama7>H/ 
Pagef  ?'.  -et 

□  Pages  >  ■    ('  .c  '  Jhr  laminated/ 
Pages  re    t    -':'■*  «t;  >u  pcllicultes 

H  Pages  dis'toiuured.  stained  or  foxed/ 
Pages  decolories.  taclteties  ou  piquees 

□  Pages  detached/ 
Pages  detachtes 

0Showthrough/ 
Transparence 


n 


Quality  of  print  varies/ 
Qualite  inigale  de  I'impression 

Continuous  pagination/ 
Pagination  continue 

Includes  index(es)/ 
Comprend  un  (des)  index 

Title  on  header  taken  from:  / 
Le  titre  de  I'en-tlte  provient: 


□  Title  page  of  issue/ 
Page  de  titre  de  la  I 

□  Caption  of  issue/ 
Titre  de  depart  de  la  li 

□  Mas  in 
Gener 


livraison 


ead/ 

Ique  (periodiques)  de  la  livraison 


^1 


22X 


26  X 


30X 


^    ! 

1 

12X 


16X 


20X 


24  X 


28X 


32  X 


i 


The  copy  filmed  here  has  been  reproduced  thanks 
to  the  generosity  of: 

Thomas  Fisher  Rare  Boole  Library, 
University  of  Toronto  Library 

The  images  appearing  here  are  the  best  quality 
possible  considering  th     ;ondition  and  legibility 
of  the  original  copy  and  in  keeping  with  the 
filming  contract  specifications. 


Original  copies  in  printed  paper  covers  are  filmed 
beginning  with  the  front  cover  and  ending  on 
the  last  page  with  a  printed  or  illustrated  impres- 
sion, or  the  back  cover  when  appropriate.  All 
other  original  copies  are  filmed  beginning  on  the 
first  page  with  a  printed  or  illustrated  impres- 
sion, and  ending  on  the  last  page  with  a  printed 
or  illustrated  impression. 


The  last  recorded  frame  on  each  microfiche 
shall  contain  the  symbol  — »•  (meaning  "CON- 
TINUED"), or  the  symbol  V  (meaning  "END"), 
whichever  applies. 

Maps,  plates,  charts,  etc.,  may  be  filmed  at 
different  reduction  ratios.  Those  too  large  to  be 
entirely  included  in  one  exposure  are  filmed 
beginning  in  the  upper  left  hand  corner,  left  to 
right  and  top  to  bottom,  as  many  frames  as 
required.  The  following  diagrams  illustrate  the 
method: 


1 

2 

3 

1 

2 

4 

5 

:i     L.  J''*ci:^:.;" 


L'exemplaire  film*  fut  reproduit  gric*  i  la 
g6r>iro*\ti  de: 

Thomas  Fishar  Rara  Book  Library, 
Univeriity  of  Toronto  Library 

Les  images  suivantes  ont  iti  reproduitas  avac  le 
plus  grand  soin,  compte  tenu  de  la  condition  at 
de  la  nettet6  de  rexemplaire  film^,  et  en 
conformity  avec  les  conditions  du  contrat  de 
filmage. 

Les  exemplaires  originaux  dont  la  couverture  en 
papier  est  imprim^e  sont  filmis  en  commenpant 
par  le  premier  plat  et  en  terminant  soit  par  la 
dernidre  page  qui  comporte  une  empreinte 
d'impression  ou  d'illustration,  soit  par  le  second 
plat,  selon  le  cas.  Tous  les  autres  exemplaires 
originaux  sont  filmis  en  commenfant  par  la 
premiere  page  qui  comporte  una  empreinte 
d'impression  ou  d'illustration  et  en  terminant  par 
la  dernidre  page  qui  comporte  una  telle 
empreinte. 

Un  des  symboles  suivants  apparaTtra  sur  la 
dernidre  image  de  cheque  microfiche,  selon  le 
cas:  le  symbole  — ►  signifie  "A  SUIVRE",  le 
symbole  V  signifie  "FIN". 

Les  cartes,  planches,  tableaux,  etc.,  peuvent  Atre 
fiimds  A  des  taux  de  reduction  diffArents. 
Lorsque  le  document  est  trop  grand  pour  dtre 
reproduit  en  un  seul  clichA,  il  est  filmA  i  partir 
de  Tangle  supArieur  gauche,  de  gauche  i  droite, 
et  de  haut  en  bas,  en  prenant  le  nombre 
d'images  nAcessaire.  Les  diagrammes  suivants 
illustrent  la  mAthode. 


2 

3 

5 

6 

MIOtOCOTY   kESOlUTION   TfST  CHART 

(ANSI  and  ISO  TEST  CHART  No.  2) 


1.0 


I.I 


12.2 


3.6 

7    12.0 


11-25  iu 


1.8 


1.6 


A  -APPLIED  INA/IGE    Inc 

^^  1653  Eosl  Main   Street 

S^JS  Rochester,   New   York        14605       USA 

'•SJS  (716)   482  -  0300  -  Ph    le 

^S  f^'^'   288  -  5989  -  fax 


;^ 


Chronic  I  fit  erst  it ia  I  Nephritis  and 
Arteriosclerosis 


BY 


OSKAR   KI.OTZ,  M.D.,  CM. 


Pr-T«BlHiiH,   PA. 


FROM  THE 

AMKKU  AN  JOl  RN.Al.  OK  THK  MKDICAI.  SCIENCKS 

DecenibtT,  191.S  No.  6,  vol.  cl,  p  ^i'l 


n.- 


Eitni  -ted  from  th>'  American  Journal  ol  the  MmlUal  Sp=ence», 
IV<«'nil)cr,  1U15,  N'li,  »l,  vol.  el,  p.  »27. 


CHROmC  INTEESTITIAL  NEPHRITIS  AND 
ARTERIOSCLEROSIS. 


By  Oskar  Klotz,  M.D.,  CM., 

PITTBBUHQH.    PA. 

(From  the  Pathologiral  Luborotoricg,  University  o.    'ittsburgh.) 


No  agreement  has  as  yet  been  reached  as  to  the  nature  of  and 
the  progressive  changes  leading  up  to  the  granular  kidney.  Almost 
all  the  factors  having  to  do  with  the  carrying  out  of  the  normal 
kidney  function,  as  well  as  the  known  factors  giving  rise  to  pro- 
cesses'of  fibrosis  in  c*her  organs,  have  been  mentioned  as  the  incit- 
ing cause  of  renal  sclerosis.  Particular  weight  has  been  placed 
upon  certain  of  these  factors,  because  of  their  presence  diiriiiL.  one 
stage  of  the  disease;  but  the  opportunity  of  weighing  their  impor- 
tance as  an  active  cause  for  the  contracted  kidney  hps  not  been 
sufficiently  good  to  direct  a  knowing  finger  at  them.  No  one  has 
yet  been  able  to  describe  in  a  single  instance  the  sequence  of  events 
from  the  beginning  to  the  fully  developed  chronic  interstitial 
nephritis.  Thus,  opportunity  has  remained  open  for  wide  specu- 
lation on  the  interpretation  of  the  pathological  processes  involved. 

Some  attempt  has  been  made  to  link  up  the  clinical  and  urinary 
findings  with  the  successive  changes  that  are  taking  place  in 
the  tissues  of  the  kidney.  These,  however,  have  added  little  to 
our  understanding  of  the  process.  True  it  is,  that  with  the  fully 
developed  disease,  certain  manifestations  make  their  appearance, 
and  we  believe  that  some  light  has  been  thrown  upon  the  correla- 
tion of  the  urinary  character  with  the  altered  functional  capacity 
due  to  renal  sclerosis.  But  as  for  saying  that  the  clinical  manifes- 
tations bear  any  relation  to  the  ructural  change  of  the  kidney 
prior  to  the  stage  of  granular  coi  paction  or,  better,  that  we  can 
forecast  the  outcome  or  even  suggest  the  past  processes  in  the 
kidney  by  clinical  analyses  we  have  no  definite  evidence. 

Thus  the  problem  has  been  left  in  the  realms  of  conjecture  and 
in  the  absence  of  incontestable  proof  by  experiment,  our  knowledge 
concerning  the  development  of  the  granular  kidney  has  not  mate- 
riallv  advanced  since  the  days  of  Gull  and  Sutton.    In  the  face  of 


2  KLOTZ:   IvrilRHllUAL  NEPHBITW  AND  ARTERIOHCLF.nOHlS 

this  we  do  not  wish  to  minimize  the  value  ot  the  many  observations 
whicli  have  jjiven  us  a  clearer  unfierstHndinK  of  some  of  the  fan'-r 
reactions  in  the  kidney  sul)stan(e;  l.ut  it  wouKl  ai)i>ear  that  the 
minutia-  t  some  of  tiiese  observations  iiave  led  us  astray  froin  the 
broad  aM,ects  of  tU  proMm.  That  Jores  should  Knd  a  splitting 
of  the  internal  elastic  latnuia  of  the  renal  arterioles,  and  from  this 
finding  discuss  the  importance  of  those  still  indefinite  factors  indue- 
infc  :>rteriosclerosis  as  of  prime  imiwrtame  for  kitlney  di-ienso,  is, 
it  seems  to  me.  quite  aside  from  the  main  issue. 

For  the  main  part,  as  was  brought  before  the  Association  of 
American   Phvsicians   last   year,   studies   upon   the   pathologu'al 
nature  of  chronic  interstitial  nephritis  have  been  made  upon  the 
ach  ance<l  form  of  the  disease.    The  criterion  fo'  the  recognition  of 
the  important  tvpe  of  the  «lisease  is  still  based  upon  the  description 
of  the  kidnev  as  given  by  Richard  H  '  -ht.    «f  we  a.lhere  clos;         . 
these  described  characters,  we  will  finu    acre  is  a  general  similu.    v 
grouping  them  into  one  class,    (iradually,  however,  our  attentioi. 
has  been  drawn  to  the  fact  that  there  are  other  forms  of  renal  sc  e- 
rosis  differing  to  a  greater  or  less  degree  from  the  type  here  under 
discussion   ami    readily    recognized    by   careful    observatum    and 
supplemented  bv  the  microscope.    Thus  we  have  kidnev  hbroses 
associated  with  hydronephrosis,  ascending  infection  of  ureter  and 
bladder,  hematogenous  infection  (pyogenic),  infarcts,  thromboses, 
amyloid  disease,  syphilis  and  other  infective  granulomata.  and 
arteriosclerosis.    But  when  we  are  speaking  of  the  small,  contractcil 
or  granular  kidnev  we  have  in  mind  a  diseased  condition  of  the 
kidnev  which  is  different  from  each  of  these.     It  is  different  not 
only  in  the  structural  changes  induced,  but  it  is  different  also  in  its 
progress  and  in  the  distant  systemic  responses.    The  small,  granular 
kidney  is  recognized  bv  its  small  size,  the  thickening  of  its  capsu.e 
with  'adherence  to  the  underlying  cortex.    The  kidne.v  substance 
when  strippeil  of  its  capsule  is  distinctly  granular,  each  granule  being 
surrounded  bv  a  depression  from  which  fibrous  tissue  radiates  par- 
allel with  the  ascending  vessels.    The  kidney  substance  may  appear 
red,  but,  on  the  other  hand,  may  be  quite  pale  with  not  a  few  ot  its 
granules  as  vellow  as  the  adrenal  cortex.   The  cc  rtex  is  most  markedly 
altered,  and  is  commonly  only  half  the  thickness  of  the  normal 
structure.     Within  it  are  found  many  fine  wedge-like  sclerotic 
areas  which  occupv  the  positif)ns  between  the  granules  observed  on 
the  surface.    Alternating  with  these  areas  of  fibrosis  a  fairly  norinal 
kidney  .issue  is  observed.     Along  the  patch  of  these  radiating 
fibroses  the  tubules  and  Malpighian  corpuscles  become  inv()lved. 
The  medulla  is  less  altered,  although  a  hyaline  fibrosis  not  intre- 
quentlv  surrounds  the  excretory  tubules.     As  in  other  regions 
subject  to  progressive  fibrosis  a  considerable  adipose  tissue  (le\  elops 
in  the  surrounding  structures,  particularly  about  the  pelvis. 
At  the  present  time,  opinion  as  to  the  development  of  this  torm 


KLOTZ:    INTERCTITIAI.   NK-IIHiriH    AM>   AHTKItlOHl  I.KIU w|H  3 

of  the  interstitial  nephritis  h«s  Im>»'h  ilividwl  rnuiniy  iMtwwii  i  o 
schools:  the  one  fonsiders  it  the  outeoine  of  a  h>w  ariulv  hut  pnn 
gressive  inHanimation,  while  the  other  l»elie\es  it  the  re-*uit  of  n 
primary  cireuhitory  distnrhnnce  with  u  seeondury  atrophy  ami 
replacement  fihrosik  Unfortunately  the  issue  has  In-en  somewhat 
eonfnse«l  hy  the  further  intro<hi<  tion  of  the  terms  primary  and 
seeontlary  interstitial  nephritis.  Kach  jjroup  clainis  that  their 
explanution  is  adecpiate  for  the  so-calle*!  >t«"'>iii"ie  eoiitraet»-<l  kid- 
ney. We  would  do  well  to  drop  such  irrelevant  terms  and  leave 
the  apjilication  of  a  new  nomenclature  to  him  who  clearly  indieates 
the  ptttholoKicul  secpietice  of  events  coneerne<l  in  chronic  interstitial 
nephritis. 

Ciull  and  Sutton  considered  the  relationship  of  the  arteries  to 
the  diseiiMS  of  the  kidneys  as  a  peculiarly  intimate  ojie  in  which 
the  arterial  processes  pre<-ede«l  and  determined  the  interstitial 
nephritis.  No  agreement  was  reachetl  hy  suhsecpient  workers  of 
the  actual  nature  of  the  arterial  disease,  some  vicwiu);  it  as  an 
endarteritis  (Thoma),  others  as  an  hypertrojjhy  (Johnson,  Kwald, 
Fricdmann),  while  the  suhsecpient  work  hy  I'rym  n-id  .lores  drew 
attention  to  the  arterial  lesion  as  a  true  arteriosclerosis,  .lores, 
furthennore,  contended  that  the  asscM-iated  a.terial  changes  in 
other  organs,  as  was  ilescrihed  h\  nany,  was  also  an  arteriosclerotic 
process.  The  differentiation  of  tlii  ))r(K-ess  rested  upon  the  finding 
of  deep  arterial  dejtenerations  associated  with  a  splitting  of  the 
internal  elastic  liner.  As  Jores,  however,  ohservcnl,  arteriosclerosis 
may  occur  in  the  arteries  of  other  organs  in  the  ahsence  of  sclerosis 
of  the  renal  vessels. 

While  the  ahovc  authors  were  contending  the  ilcpendence  of 
chronic  nephritis  ui)on  disease  of  the  hlovMlves.sels.  Zieglcr  main- 
ta'  -ed  the  differentiation  of  types  of  chronic  nephritis  into  iiroups 
associated  or  nTi,.s.sociated  with  arteriosclerosis.  Those  kidney 
lesions  resulting  from  nrterio.sclerosi-  he  hclieved  to  he  individual 
and  of  a  ])urely  degenerative  character,  and  designated  them  the 
arteriosclerotic  kidney. 

Both  Jores  and  his  pupils  repeatedly  remarked  that  dironic  nucr- 
stitial  nephritis  is  a  disease  most  frecpiently  encountered  in  advanced 
life,  a  period  when  arteriosclerosis  is  also  most  prevalent.  Never- 
theless, they  remark  upon  the  finding  of  occasional  cases  in  which 
they  have  been  able  to  demonstrate  ar'vanced  renal  sclerosis  unac- 
companied by  arteriosclerosis  within  the  kidney.  This  agrv  s  with 
the  finding  c.f  Orth,  who  believes  that  in  chronic  interstitial  nephritis 
the  vascular  changes  are  not  essential  because  their  Vc-'iety  does 
not  correspond  with  the  extent  of  the  lesions.  Roth  dt  rihed  a 
number  of  cases  in  which  renal  sclerosis  was  advanced,  but  in 
which  the  arteries  did  not  show  the  type  of  sclerosis  defined  by  -lores 
as  arteriosclerosis.  He  did,  however,  find  that  the  arteries  were 
affacted  I      a  connective-tissue  thickening  of  the  intima  with 


4  KUrrZ:   INTERKriTIAL  NKPIIRITIB  AND  ARTERlOSCtEROSW 

splitting  of  the  elastic  lamina.  As.  however.  |.n.ces8e9  of  (WiMieni- 
tion  were  wanting,  he  refuse<l  to  call  it  arteriosclenwis.  Me  Mim'-ts 
that  the  <■  vessels  might  »uhse«,uently  show  artcrioscler«)tic  cluuiKf 
Fron.  his  obsenati.ms  we  can  only  comliule  that  the  kidiM  y  lesions 
have  advance«l  with  greater  rapidity  than  those  m  tin  intima  of 
the  renal  vessels,  and  his  casts  illustrate  tht  point  we  wish  to  nrnke 
that  the  narrowlv  definecl  Umn  of  arteri()s«leros\s  as  given  Jores 
is  not  an  essential  factor  in  brinKing  out  snl.sequent  n»terstitia! 

"Tloth  de8cril>e<l  3  cases  of  chronic  interstitial  rephritis  without 
arteritwclerosis.  In  the  kidneys,  however,  endarteritis  was  present 
in  the  small  arteries.  The  cases  were  of  relatively  yc.ung  individ- 
uals and  all  of  tl.em  had  definite  chronic  or  recurrent  lieart  aii<l 
arterial  discuses.  Yet  with  it  all  neither  .lores  nor  his  pupil  s.m's 
anv  direct  relationship  insofar  as  a  common  causative  fuct.jr  is 
.•..luerned  in  the  simultaneous  ami  progr.  4ve  lesions  -u  these  three 
organs  These  authors  lav  much  stress  on  the  finding  of  a  single 
stlemscd  arteriole  or  the  mildest  beginning  of  intimal  degeneration 
as  indicative  of  the  influence  of  arteriosclerosis  uiwn  the  kidney. 
N(.  recognition  is  given  to  the  fact  expressed  Im  their  own  cases 
that  the  fibrosis  of  the  kidney  wa"  marke<liy  advanced,  and  in  the 
late  stages  of  contraction,  while  the  arteriosclerosis  xyas  only 
iH-ginning.  We  can  in  no  way  follow  the  conclusion  of  tins  author 
as  illustrated  by  his  own  cases  that  the  chronic  interstitial  nephritis 
was  the  result  of  the  early  endarteritis  demonstrated. 

In  the  admirable  work  of  Councilman  (!Sn7)  the  part  playc( 
bv  the  inflammatory  process  in  bringing  alwut  the  interstitial 
lesions  of  the  cortex  of  the  kidney  was  well  demonstrated,    in  part, 
the  cii^es  studied  included  some  of  scarlet  fever,  diphtheria,  pneu- 
monia, and  other  infections,  and  the  lesions  described  wrre  ot 
the  nature  of  diffuse  non-suppurative  interstitial  nephritis  or  t.vi)es 
of  glomerulonephritis.    Of  the  latter,  two  fonn    were  distinguished: 
a  non-suppurative  exudative  form  and  a  proliferate  e  type.     -No 
clear  distinction  can  b«>  made  between  the  etiological  factors  present 
in  these  two  tvpes.  and  it  would  sc.m  that  both  may  arise  from  the 
same  causativ^  factor.    At  the  time  of  carrying  out  his  work,  bac- 
teriological methods  were  not  available  to  ma  ke  a  <listinction  between 
the  various  forms  of  streptococci,  and  we  find  the  author  siu-aking 
of  the  organisms  isolated  from  cases  of  he«-^  disease  as  pncumococci. 
I  believe  we  will  be  correct  in  interpreting  these  results  as  indicating 
the  presence  of  the  Streptococcus  viridans  group.    These  organ- 
isms were  found  in  cases  of  glomerulonephritis  in  large  percentage, 
but  the  author's  descriptions  of  the  lesions  indicate  a  transition 
between  the  glomerulonephritis  and  the  diffuse,  interstitial  type. 
The  work  of  Wagner  bears  out  these  findings,  particularly  in 
indicating  the  importance  of  the  inflammatory  process  of  scarlet 
fever  and  other  infections  in  bringing  about  permanent  interstitial 
change. 


Muyn:  intebhtitui.  nephmitw  and  \kt»' 


MIHIW 


The  work  of  CouncilniHti  is  atnoiiK  tlic  (vw  in  wiiioli  it  stmly  of 
the  progressive  lesiutis  of  the  kidnt-y  was  areuinpanieil  hv  ha«'terio- 
logical  examination.  (M  this  he  suys:  "Various  forms  of  ili.scast> 
of  «)ther  organs,  particularly  of  the  heart,  are  often  ass<Kiutetl  with 
them,  and  Iwcteriohtgical  investigatiuti  has  fre<pieiitly  shown  in 
mm  y  cases  the  presence  of  .-rtain  organisms  in  the  kidneys.  In 
mo>f  cases  the  bu«teriii  are  found  in  sunie  other  lesion  and  in  the 
bl«HKl,  and  their  presence  in  the  kidneys  is  but  a  part  of  a  general 
septicemia.  Moreover,  the  same  ctmditimis  in  the  kiilneys  may  Ih: 
found  associated  with  various  orgtnisms,  and  the  same  organisms 
may  be  associatetl  with  widely  different  anatonii  al  lesions."  A 
very  fertile  iield  awaits  the  routine  study  of  the  bacteriology  of  the 
kidneys  in  conjunction  with  the  histological  examination  of  all 
types  of  infc  .>n.  The  wor'  -vhi'-h  has  U-en  i)erformed  up  to  the 
present  time  is  very  sugges  of  indicating  the  actual  pres«'nce 
of  bacteria  rather  thru  their  •  ns  in  the  interstitial  res|M)nsc  of  the 
kidney. 

Undoubtedly  wh..  O'/jK-ars  as  complete  disagreement  ii  the 
persona^  •  Sser\  atioi  ■  .  chronic  nephritis  lies  mainly  in  the  mcthtxls 
and  ma  i  I  sludieu.  Although  the  iiiuitomical  classification  of 
kiihiey  i..:.case  has  not  fo'ind  favor  with  either  the  clinician  or  the 
pathologist,  yet  in  the  absence  of  a  better  substitute  we  all  revert 
to  this  methotl.  Miiller  attempted  un  etiological  classification  which 
as  yet  is  hardly  practical,  and  Ilerrick,  while  finding  the  old  ana- 
tomical grouping  unsatisfactory,  offers  nothing  to  replace  it. 

The  tyiH-'s  of  nephritis  whic"i  totlay  attract  our  attention  as  the 
forerunners  of  the  contracted  kidney  are  the  acute  glomerulo- 
nephritis and  the  acute  non-suppurative  interstitial  nei)liritis. 
Without  desiring  to  describe  the  various  tyi)es  of  gU)meruh)nepliritis, 
as  well  as  the  variety  of  interesting  lesions  that  niaj-  l)e  observed 
in  the  Malpighian  body  and  Bowman's  capsule,  there  is  ample 
evidence  that,  in  t'  :  human,  these  glomerulonephritides  are  infec- 
tive lesions  (Councilman,  Guskeil,  Baehr).  The  imiK)rtant  feature 
lies  in  the  fact  that  the  glomeruli  become  the  centres  of  inflamma- 
tory response  in  which  a  non-suppurative  exudate  and  endothelial 
proliferation  of  the  capillaries  and  a  proliferative  resjionse  of  the 
inner  lining  of  the  capsule  is  commonly  observed.  The  occlusion  of 
the  capillaries  of  the  glomeru)"s  by  cellular  proliferation  or  by 
thrombosis  is  only  an  added  complication,  and  the  subsequent 
degeneration  that  occurs  in  the  tubules  of  the  kidney  is  also  to  be 
viewed  as  a  secondary  disturbance  depending  upon  vascular  change 
rather  than  an  injury  produced  by  the  primary  factor. 

A  study  of  these  i  les  of  glomerulonephritis  soon  convinces  one 
of  the  varying  picture,  even  during  the  acute  stage.  In  some 
thromboses  of  the  glomeruli  are  common,  in  others  rare,  or  the 
lymphocytic  infiltration  of  the  glomerulus  is  great  and  confined  to 
this  structure;  others  again,  show  the  inflammatory  reaction  diffuse, 


6  KLOTZ:  INTERSTITIAL  NEPHRITIS  AND   ARTERIOSCLEROSIS 

surrounding  Bowman's  capsule,  infiltrating  the  stroma  between 
Se  tubulef  and  following  the  course  of  the  mterlobular  artenes 
and  vessels  of  the  intermediate  zone.  Many  such  cases  have  been 
descriS  by  Councilman,  Ziegler,  and  others.  In  fact,  the  p'cture 
nresented  by  those  kidneys  in  which  the  mflammation  is  more 
diffuse  simulates  more  closely  the  type  of  acute  mterstit.al  non- 
suppurative nephritis.  This  latter  type,  which  was  originally 
diSsed  as  a  disease  of  the  kidneys  found  after  scarlet  fever 
measles,  and  sometimes  smallpox,  is  ..  v  being  incorporated  ..ith 
the  glomerulonephritis,  mainly  because  a  certain  amount  of  glomer- 
ular disturbance  is  always  present.  Fahr  finds  the  streptococcus  and 
pneumococcus  most  frequently  associated  with  acute  interstitia 
nephritis,  and  finds  also  that  the  same  organisms  are  the  chief 
cause  of  glomerulonephritis.  ,     i    •  j 

In  short,  although  there  are  variations  of  glomerular  lesions  and 
we  encounter  forms  of  inflammation  of  the  kidney  stroma,  there 
does  not  appear  to  be  any  difference  in  the  causative  agent,  most 
frequently  the  Streptococcus  viridans.    We  must,  however,  point 
out  that  the  bacterial  infection  reaches  the  kidney  under  different 
circumstances,  and  in  a  somewhat  different  form,  in  the  various 
™emic  diseases  in  which  it  is  met.    It  is  the  bacterial  clusters 
or  small  infective  thrombotic  masses  which  are  liberated  in  he.  rt 
disease  that  give  rise  to  a  type  of  glomerular  infarction,     in 
this  wav  particular  structures  in  the  kidney  are  more  intensely 
involved  than  others.    So.  too,  in  cases  of  bacteriemia,  by  organ- 
isms of  low  virulence,  the  kidney,  as  well  as  other  organs,  becomes 
a  local  focus  of  infection  and  this  is  particularly  tnie  in  the  bacterie- 
mia of  acute  rheumatic  fever  in  which  the  heart  and  bloodvessels 
are  also  affected.     In  these  infections  the  heart  may  be  involved 
in  a  variety  of  ways,  and  when  the  endocarditis  becomes  well- 
marked  the  kidney  may  be  subject  to  embolic  processes  m  its  glo- 
meruli, so  that  both  the  acute  interstitial  and  the  glomerulonephritis 
are  simultaneously  prominent.    Hence  it  is  obvious  that  to  state 
that  a  definite  tvTC  of  kidney  lesion  is  constantly  to  be  found  as  a 
disease  associate  with  infection  of  other  organs  is  only  voicing  a 
rule  with  prominent  exceptions. 

The  frequency  with  which  acute  interstitial  and  glomerulo- 
nephritis are  present  with  infective  heart  disease  is  known  to  all 
who  have  observed  these  cases  at  autopsy  and  studied  the  tissues. 
It  is,  furthermore,  easy  to  demonstrate  the  fate  of  the  early  mflani- 
matorv  process.  Fibroses  of  the  glomeruli,  of  Bowman  s  capsules, 
and  of  the  intertubular  stroma  may  be  demonstrated  in  all  stages 
of  formation,  and  recurrent  attacks  of  these  infective  processes  give 
rise  to  combinations  of  inflammatory  responses  in  the  kidney  tissues. 
The  question  immediately  arises  whether  the  localization  of  these 
inflammatory  processes  gives  us  definite  types  w^hereby  their 
futur"  scars  mav  be  recognized.   In  answer  to  this  the  best  reference 


KLOTZ:  INTERSTITIAL  NEPHRITIS   AND  ARTERIOSCLEROSIS  7 

is  made  to  a  few  experimental  results.  In  these  it  has  been  shown 
that  inflammatory  reactions  in  the  kidney  due  to  bacterial  agents 
are  prone  to  follow  and  surround  the  course  of  the  bloodvessels 
particularly  the  interlobular  vessels,  and  the  ascending  cortical 
branches  as  well  as  the  afferent  arteries  of  the  glomeruli.  Asso- 
ciated with  these  inflammatory  responses  there  are  not  infrequently 
glomerular  reactions,  infiltrative,  proliferative,  or  thrombotic. 
The  progress  of  these  lesions  is  similar  to  that  in  the  human  kidney 
and  the  end-result  is  a  process  of  fibrosis  radiating  in  its  character 
with  shrinking  and  granulation  of  the  cortex  and  contraction  of 
the  entire  kidney.  Such  lesions  were  reproduced  in  animals  by  the 
use  of  organisms  (various  members  of  the  Streptococcus  viridans 
group)  isolated  from  infective  heart  disease,  and  the  responses  in 
the  kidney  were  found  to  be  accompanied  by  a  myocarditis,  at 
times  an  endocarditis,  and  in  a  few  cases  pericarditis.  In  only  a 
few  instances  were  systemic  intimal  arterial  lesions  obtained, 
although  the  perivascular  response  was  always  noted.  Here,  then, 
we  have  evidence  of  the  development  of  the  various  stages  of  the 
contracted  kidney  in  the  presence  of  chronic  infection  and  in  the 
absence  of  primary  arterial  lesions. 

These  findings  are  in  accord  with  the  observations  on  human 
material  and  explain  the  occurrence  of  the  contracted  kidney  in  the 
first  half  of  life  as  well  as  its  greater  frequency  in  the  later  years. 
L'We  all  chronic  diseases,  the  frequency  of  chronic  interstitial 
nephritis  is  greatest  in  the  late  decades,  and  it  is  also  a  rather 
depressing  outlook  when  we  find  that  the  incidence  of  these  chronic 
diseases  shall  increase  with  the  saving  of  more  lives  in  childhood 
from  death  from  scarlet  fever,  acute  rheumatic  fever,  chorea,  and 
other  Streptococcus  viridans  infection.  We  must  also  equally 
appreciate  that  the  heart  and  arteries  suffer,  sometimes  much,  at 
other  times  less,  by  invasion  of  these  bacteria.  In  the  arteries  an 
endarteritis,  a  mesarteritis,  and  a  periarteritis  have  all  been  r<ipeat- 
edly  demonstrated  in  these  infections  during  the  early  years  of  life. 
Of  the  heart  lesions,  we  need  make  no  other  comment  than  rei'erence 
to  Aschoff's  studies  upon  focal  myocarditis,  and  of  the  f -equent 
presence  of  endocarditis  in  the  human  and  in  experimental  infec- 
tions. 

What,  then,  is  the  relation  of  renal  arteriosclerosis  to  chronic 
interstitial  nephritis?  Before  one  can  answer  this  we  :r "  have 
a  clear  understanding  of  the  nature  and  genesis  of  arteriosclerosis. 
It  is  not  enough  to  boldly  speak  of  general  arteriosclerosis  as  of 
common  type  and  constant  origin.  Nor  is  this  true  v.ithin  the 
kidney  itself.  There  are  arterial  lesions  within  the  kidney  whose 
origin  is  widely  different  and  which  vary  in  their  character. 

Ziegler  has  long  ago  demonstrated  the  peculiar  renal  fibrosis 
resulting  from  peripheral  arteriosclerosis.  In  old  age,  where  it  is 
not  uncommon  to  have  various  arterial  tracts  severely  involved  in 


PA:^^^£r-^.\^&:->~ 


1:<S««~te3^5< 


8  KLOTZ:  IXTERSTITIAL  NEPHBITIS  AND  ARTERIOSCLEROSIS 

sclerosis  and  in  which  the  lumina  of  the  vessels  are  ftinMy 
imSd,  atrophic  changes  result  in  the  area  supplied.     It  is 
Kous  hat  the  amount  of  sclerosis  varies  greatly  and  is  bound  to 
S  out  limited  areas.    The  kidney  tissues  which  suffer  from  the 
&atory   disturbances   undergo   atrophy,   and   even   complete 
™  Sthout.  however,  necessarily  showing  evidence  of  intra^- 
u  ar  degeneration  (fat),  as  is  otherwise  so  commonly  encountered. 
S  kidney  Aows  ar.:;s  of  sharp  depressions  scattered  irregulariy 
ov?r  its  surface  so  thai  .ts  structure  and  shape  are  distorted.    The 
indTv  durdepressions  simulate  those  of  infarct,  bu    microscopic- 
aUv  may  at  times  be  distinguished  from  these  in  that  the  involved 
areas  contain  some  of  the  parenchymatous  structures  not  com- 
Sly  de  troyed .   Furthermore,  the  kidney  capsule  is  rarely  adher- 
er.' and  the  cortical  surface  between  the  areas  of  depression  is 

tuSe^eSons  are  the  result  of  the  obliteration  of  Mrly  la^ge 
vessels  within  the  kidney.  At  times,  it  may  be.  smaller  vessels 
invdvlng  more  restricted  portions  of  the  kidney  are  affected 
This  then,  leads  to  a  local  fibrosis  of  the  glomeruli  supplied  by  this 
ciSation  Under  these  conditions  the  process,  both  m  he  glom- 
eridi  and  tubules,  is  one  of  slow  and  progressive  degeneration  with 
a  secondary  replacement  fibrosis.  It  is  unusual  to  observe  under 
these  conditions  any  evidence  of  an  inflammatory  reaction. 

Smp  ed  with  the  gr«  alar  contracted  kidney  these  changes 
in  trarteriosclerotic  kid,  y  are  quite  different.  It  is  inconceiv- 
able that  a  process  of  arteriosclerosis  could  so  ""'"^  ^^f  *  ^^ 
manv  arterioles  of  a  constant  caliber  to  give  the  character  found 
Tthe  uniformly  granular  kidney.  A  comparable  picture  is  to  be 
ob  erved  n  n'^  part  of  the  body,  and  we  are  wdl  a^va^e  how  uncer- 
tain is  the  distribution  of  arteriosclerosis.  As  the  fibrosis  fol  owing 
upon  processes  of  degeneration  in  the  atrophies  of  vascular  scleroses 

b'wXut  inflammatory  response,  one  -\--.-^*-^^,fXe:fn 
of  a  granulation  tissue  and  subsequent  adhesions  The  absence  of 
the' e  is  noted  in  the  freedom  of  the  kidney  capsule  and  in  the  lack 
of  vnechi.^  about  the  glomerulus.  Frequently  too,  Bowmans 
capsule  shows  no  thickening.    Ziegler  truly  calls  this  the  .enile 

'"Itb,"  however,  not  common  to  meet  with  a  clear-cut  and  uncom- 
plicated case.  The  vascular  scleroses  of  the  kidney  are  most  com- 
monlv  the  result  of  the  same  influence  which  has  produced  a  pri- 
ma?v  inflammatory  lesion  in  the  kidney  stroma.  Hence,  the  devel- 
opment of  scar  tissue  in  the  renal  siructures  goes  hand  in  hand 
S  lal  arter.osclerosis.  Here,  however,  in  the  early  stage,  as 
well  as  during  the  years  of  progressive  involvement  the  kulnej 
tissue  and  arteries  show  the  presence  of  inflammation.  These 
nflammatory  deposits  are  easily  recogmzed,  and  obvious  y  vary 
in  amount  at  the  different  stages.   Jores  has  seen  them  in  his  inter- 


KLOTZ:  INTERSTITLVL  NEPHRITIS  AND  ARTERIOSCLEROSIS  9 

stitial  nephritis,  but  has  taken  the  view  that  no  relation  l.etween 
the  arterial  disease  and  the  inflammation  can  be  determmed.    Like 
the  resuhs  of  the  Streptococcus  viridans  infection  upon  the  heart, 
giving  rise  to  inflammatory  processes  differently  disposed,  so  too, 
?his  Ime  infection,  which  is  so  frequently  at  the  bottom  of  the 
fibrosis   of   the   contracted   kidney,    brings   about    inflammatory 
reactions  of  varying  intensity  in  different  portions  of  its  structur^ 
The  arteries  appear  to  form  the  centre  of  distribution  for  the^ 
reactions,  and  much  of  the  response  is  spent  in  the  tissue  surround- 
ing the  small  vessels  coursing  through  the  cortex     To  a  certain 
e^rtent,  however,  intimal  reactions  are  also  found.     The  latter, 
however,  arise  somewhat  later  in  the  course  of  the  kidney  disease 
so  that  examples  are  not  difficult  to  demonstrate  in  which  intimal 
sclerosis  is  wanting  while  a  non-suppurative  inflammation  is  active 
about  the  vessel.    Later,  however,  the  picture  is  reversed  and  the 
intimal  sclerosis  attracts  our  eye.     This  is  now  the  stage  w^n 
appearances  suggest  that  a  close  relation  of  cause  and  effect  exists 
between  the  intimal  arteriosclerosis  and  the  renal  fibrosis. 

The  intimal  disease  of  the  arteries  most  commonly  met  with 
in  the  late  stages  of  chronic  interstitial  nephritis  consists  of  a 
chronic  endarteritis  with  deep,  fatty  change.  The  presence  of  a 
true  hyperplasia  of  the  musculo-elastic  layer  ^ylth  secondary 
degeneration  of  the  inner  muscle  bundle  has  never  been  met  with 
bv  us  nor  have  its  advocates  ever  clearly  demonstrated  its  pres- 
ence. The  finding  of  splitting  of  the  internal  elastic  lamina  is 
now  found  to  have  no  specific  bearing  on  the  problem  of  arterio- 
sclerosis. McMeans  (of  our  laboratory)  has  shown  that  sucli 
splitting  is  the  common  occurrence  during  inflammatory  reactions 

of  the  intima.  ,  .  i  ■  u  i     i  +„  +1,0 

Granted,  therefore,  that  the  early  reactions  which  lead  to  the 
granular  contracted  kidney,  simultaneously  involve  portions  ^  the 
kidney  parenchj-ma  and  its  arteries,  it  is  often  extremely  difficidt 
to  distinguish  in  the  late  stages  of  the  disease  exactly  how  much  of 
the  scar  tissue  has  resulted  through  inflammation  or  as  replacement 
fibrosis  following  arteriosclerotic  atrophy.  We  should,  howeNer 
continue  to  distinguish  clearly  the  arteriosclerotic  kidney  of  Ziegier 
from  the  granular  interstitial  nephritis,  the  former  giving  rise  to 
true  atrophic  processes  in  the  parenchyma  v,jth  replacement  fibrosis 
the  latter  having  an  inflammatory  basis  for  the  development  of 
connective  tissue  variously  distributed  about  the  important 
structures  of  the  organ. 


I».'.-,.T 


THE  AMERICAN  JOURNAL 

OF  THE  MEDICAL  SCIENCES 

Edited  by  George  ISIohris  Piersol,  M.D.    Monibly.    Illustrated.    1920  pag- » 

yearly.     Pri',-e,  $').00  per  annum. 

nniE  AMEUICAN  JOURNAL  OP  THE  MEDICAL  SCIENCES,  founded  in  1820.  l.» 

1    i;,^  1. rooognizod  a8  the  leading  medical  journ  J  of  the  Knghsh-spoakinR  race.    Fr.„n 

rhe  tirst  it   sought  the  efK)ch-makinK   papers,  a.ul   becominR  rrcogiiizf,!   as  the.r  ine<lmm, 

t  h.u    in  tun,    l.ecn  8<mpht  by  those  who  have  ha.1  discovenes  or  red  advances  m  the 

Jrt  an.1    c  e..;  of  n.e.iicino  to  announce  in  its  Depart.nent  of  Onpnal  Artu.les.     Ounng 

mS   ne  Am^Tuan  Joun^al  will  still  further  develop   a  feature  that  has   provr.l  n,.rt 

useft.l  and   popular,  na>,>ely,  a  .cries  of  Special  Articles,  wntten   by  prearranRement  wMh 

men   ..f   the   highest   authority,  and   covering   present-day    topics  of  the  greatest  imp-r- 

^ncc  an.i  interest.     These  articles  are  designed  to  be  clinical  and  pra.n.cal,  and  to  pre«.nt 

mportm,    advances  an.i  the  latest  knowledge  clearly  and  cone  sely,  w>th  porfcular  referenoe 

o  app      tion  in  daily  work.    The  Department  of  Book  Reviews  wdlcontmue  to  compr.se 

Ht  cal  a  d  discrin,inuting  estimates  of  irafKirtant  new  books,  as  well  as  bnefer  notices  of  book, 

of  less  in.portance  and  of  new  e-iit^ons.     The  Department  of  Progress  of  Medical  Sc  enoe 

under  the  charge  of  recognize*!  specialists,  will  cont_  nue  to  summarize  thr  actual  a.lvanccs  la 

the  art  and  science  of  medicine  appearing  in  the  leadmg  medical  p  riodicala  of  the  world. 


PROGRESSIYE  MEDICINE 

A  QUARTERLY  DIGEST  OF  ADVANCES,  DISCOVERIES  AND  IMPROVEMENTS 
IN  THE  MEDICAL  AND  SURGICAL  SCIENCES,  COVERING  THE  ENTIRE  DOMAIN 
OF  MEDICINE.  Edited  by  Hodart  Amory  Hare,  M.D.,  Professor  of  Therapeutics 
•n  Jefferson  Medical  College,  Philadelphia;  Physician  to  the  Jefferson  Medical  Collecc 
Hospital,  etc.  Assisted  by  Leighton  P.  Afpleman,  M.D.,  Instructor  in  Therapeuti.s, 
Jefferson  Medical  College,  Philadelphia.  In  four  octavo  volumes,  containing  1200  pages 
amply  illustrated.  Annual  subacription  price,  in  heavy  paper  covers,  $6.00,  net;  in  clot 
binding,  $9.00,  net.    Carriage  paid  to  any  address. 

PROGRESSIVE  MEDICINE  is  ihe  story  of  the  progress,  discoveries  and  improvements 
in  the  various  branches  of  the  m.^ieal  and  surgical  sciences,  ana  is  p.ibhshed  four  tunes 
a  vear  in  March,  June,  September  and  December.  The  matter  presentcl  is  the  d.ges  e,i 
L^nce  of  the  en  ire  medical  hterature  of  the  world  published  during  the  previous  twelve 
3«,  modifier!,  explained  and  criticised  in  the  Ught  of  the  personal  ex,H;r,ence  of  the  con- 
rbuto;  By  tliis  method  useless  information  is  discarded  and  only  that  which  is  valuable  ar.,1 
reallv  helpful  to  .he  practitioner  is  retained.  Practicality  and  thoroughness  are  t  he  controlling 
'eaturcs.  The  contributors  are  authorities  in  their  respective  lines,  and  their  experience  in 
Private  and  hospital  practice  enables  them  to  choose  unerringly  that  which  their  brother 
worker  rvi."re  Every  article  is  original,  the  veritable  product  of  the  author  whose  name 
It  beirs  The  style  is  narrative  in  form,  hence  easy  to  read.  The  interpretation  o  the  fart, 
stated  is  given  and  their  bearing  upon  the  whole  subject  under  consiu.ration  is  clearly  and 
mmply  indicated. 

COMBINATION  RATES 

The  A.mf.uicanJouknal  OP  THE  Medical  Sciences per  annum,  $5  00 

PRoonK-ssivE  Medicine  (heavy  paper  covers) ,,  °^ 

Phogbbssivb  Medicine  (cloth  binding)      •     •     •     ■      •    ,•     '     "  ..  ,« |vj 

Pboghessive  Medicine  (paper  covers)  and  the  American  Journal  W  W 


PHILADELPHIA 
Toe-«  10  aANSOM  St 


LEA  &  FEBIGER 


NEWYOfW 

a  WBST  4aTH  ST 


